This week, as pot stock Tilray jumped 50 percent, Novogratz said he "tried real hard" and found a "cool way" to short it.

"The companies trade up to $28 billion on almost no revenue," he said. "If I was long them, I'd sell them and if you're a speculator, I'd get short them."

Bitcoin, which Novogratz has been a vocal investor in, similarly shot up by double-digit percentages last year. The cryptocurrency has plummeted 66 percent since its high, according to data from CoinDesk.

Novogratz is hardly the only one betting against the cannabis craze. Data from S3 Partners show that short interest in Tilray is around 3.5 million shares, up from about 2.5 million late last month.

This week was an expensive time to bet against the stock. Fees for borrowing Tilray stock, which you need to do to short it, were between 500 and 700 percent, according to S3's managing director of predictive analytics Ihor Dusaniwsky.

Still, Novogratz is optimistic on the industry long-term and predicted the entire "cannabis business is going to grow, and it's going to grow relatively rapidly."

Novogratz launched his crypto merchant bank Galaxy Digital in November, a month before bitcoin hit its all-time high near $20,000. The firm took a $134 million hit in the first quarter of this year, according to its first-ever financial disclosure released in Canada after the company went public.

The former Fortress hedge fund manager told CNBC in November that bitcoin could "easily" hit $40,000 by the end of 2018. He also predicted ethereum, which was trading near $211 this week, could hit roughly $1,500.

Those two cryptocurrencies have gone the opposite direction. Bitcoin is down more than 50 percent this year after starting 2018 above $14,000. Ethereum meanwhile has dropped 83 percent from its high in January, according to CoinDesk.